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Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study
BACKGROUND: Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585480/ https://www.ncbi.nlm.nih.gov/pubmed/34515027 http://dx.doi.org/10.7554/eLife.68671 |
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author | Si, Jiahui Yang, Songchun Sun, Dianjianyi Yu, Canqing Guo, Yu Lin, Yifei Millwood, Iona Y Walters, Robin G Yang, Ling Chen, Yiping Du, Huaidong Hua, Yujie Liu, Jingchao Chen, Junshi Chen, Zhengming Chen, Wei Lv, Jun Liang, Liming Li, Liming |
author_facet | Si, Jiahui Yang, Songchun Sun, Dianjianyi Yu, Canqing Guo, Yu Lin, Yifei Millwood, Iona Y Walters, Robin G Yang, Ling Chen, Yiping Du, Huaidong Hua, Yujie Liu, Jingchao Chen, Junshi Chen, Zhengming Chen, Wei Lv, Jun Liang, Liming Li, Liming |
author_sort | Si, Jiahui |
collection | PubMed |
description | BACKGROUND: Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population. METHODS: We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10 year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module. RESULTS: After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate [FDR] < 0.05 or module-specific FDR < 0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47 % decrease to a 118 % increase. Mediation analyses revealed 28.5 % of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of ANKS1A gene (P for mediation effect = 0.036). Methylation level at the promoter region of SNX30 was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7 % (P = 0.003) via systolic blood pressure and 6.4 % (P = 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD. CONCLUSIONS: We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and blood pressure-related pathways to CHD risk. FUNDING: This work was supported by National Natural Science Foundation of China (81390544 and 91846303). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01). |
format | Online Article Text |
id | pubmed-8585480 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-85854802021-11-15 Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study Si, Jiahui Yang, Songchun Sun, Dianjianyi Yu, Canqing Guo, Yu Lin, Yifei Millwood, Iona Y Walters, Robin G Yang, Ling Chen, Yiping Du, Huaidong Hua, Yujie Liu, Jingchao Chen, Junshi Chen, Zhengming Chen, Wei Lv, Jun Liang, Liming Li, Liming eLife Epidemiology and Global Health BACKGROUND: Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population. METHODS: We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10 year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module. RESULTS: After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate [FDR] < 0.05 or module-specific FDR < 0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47 % decrease to a 118 % increase. Mediation analyses revealed 28.5 % of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of ANKS1A gene (P for mediation effect = 0.036). Methylation level at the promoter region of SNX30 was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7 % (P = 0.003) via systolic blood pressure and 6.4 % (P = 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD. CONCLUSIONS: We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and blood pressure-related pathways to CHD risk. FUNDING: This work was supported by National Natural Science Foundation of China (81390544 and 91846303). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01). eLife Sciences Publications, Ltd 2021-09-13 /pmc/articles/PMC8585480/ /pubmed/34515027 http://dx.doi.org/10.7554/eLife.68671 Text en © 2021, Si et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Epidemiology and Global Health Si, Jiahui Yang, Songchun Sun, Dianjianyi Yu, Canqing Guo, Yu Lin, Yifei Millwood, Iona Y Walters, Robin G Yang, Ling Chen, Yiping Du, Huaidong Hua, Yujie Liu, Jingchao Chen, Junshi Chen, Zhengming Chen, Wei Lv, Jun Liang, Liming Li, Liming Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
title | Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
title_full | Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
title_fullStr | Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
title_full_unstemmed | Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
title_short | Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study |
title_sort | epigenome-wide analysis of dna methylation and coronary heart disease: a nested case-control study |
topic | Epidemiology and Global Health |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585480/ https://www.ncbi.nlm.nih.gov/pubmed/34515027 http://dx.doi.org/10.7554/eLife.68671 |
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